The health of the oral cavity is maintained by salivary secretions. Our past studies have focused on understanding mechanisms of saliva formation and their alteration during pathologic processes. During this reporting period we have continued our efforts to utilize gene transfer technology to alter the phenotypic behavior of salivary epithelial cells. Specifically, we have continued efforts to correct the salivary damage suffered by patients whose salivary glands are exposed to radiation during treatment for head and neck cancer. We have extended past in vitro findings and shown that delivery of a recombinant adenovirus encoding aquaporin-1 to irradiated salivary glands in rats can lead to increased fluid secretion to near normal levels. Secondly, we have also extended studies on the systemic secretion of transgene products from transduced salivary epithelial cells. We showed that glands infected with a recombinant adenovirus encoding human growth hormone secrete therapeutic levels of functional hormone in adult rats. We also have demonstrated that administration of recombinant adenoviruses to rat salivary glands does not result in significant systemic toxicity.